Edible film for transmucosal delivery of nutritional supplements

ABSTRACT

In one embodiment of the present invention a composition is provided comprising a film layer wherein the film layer rapidly dissolves in an oral cavity and a coating comprising a powder matrix, wherein the coating is applied to at least one side of the film layer and wherein the powder matrix comprises a nutritional supplement, an adhesive, a bulking agent, a flow agent, and a sweetener.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims priority to: (a) U.S. Provisional PatentApplication No. 60/677,679, filed May 3, 2005 (Atty Dkt No.57778.8005.US00), (b) U.S. Provisional Patent Application No.60/677,717, filed May 4, 2005 (Atty Dkt No. 57778.8005.US01), (c) U.S.patent application Ser. No. 10/713,544, filed Nov. 14, 2003 (Atty DktNo. 57778.8001.US01), which claims priority to U.S. Provisional PatentApplication No. 60/426,598, filed Nov. 14, 2002 (Atty Dkt No.57778.8001.US00), and U.S. Provisional Patent Application No. 60/497,186filed Aug. 22, 2003 (Atty Dkt No. 57778.8003.US00), (d) U.S. patentapplication Ser. No. 10/402,273, filed Mar. 28, 2003 (Atty Dkt No.57778.8002.US00), (e) U.S. patent application Ser. No. 10/921,770, filedAug. 18, 2004 (Atty Dkt No. 57778.8003.US01), which claims priority toU.S. Provisional Patent Application No. 60/497,186, filed Aug. 22, 2003(Atty Dkt No. 57778.8003.US00), and (f) U.S. patent application Ser. No.10/706,810, filed Nov. 12, 2003 (Atty Dkt No. 57778.8004.US00), whichclaims priority to U.S. Provisional Patent Application No. 60/426,598,filed Nov. 14, 2002 (Atty Dkt No. 57778.8001.US00), the disclosures ofall of which are incorporated by reference herein in their entirety,including drawings.

FIELD OF THE INVENTION

The present invention relates to the use of edible films fortransmucosal delivery of nutritional supplements.

BACKGROUND OF THE INVENTION

There is a long history of human consumption of vitamins, minerals,herbs, and other nutritional substances. The health food industry mightbe considered to have emerged in the 1800s with Reverend SylvesterGraham's invention of the Graham cracker and Kellogg's development ofpackaged cereals.

By the middle of the 20th Century consumers were encouraged to consumethree nutritional meals a day and to avoid foods with negative effectson the body. Emphasis in the latter part of the Century shifted fromavoidance of food with negative effects on the body to monitoring thequantities consumed. It was at this time that advances in science andmedicine accelerated the understanding and popularity of functional foodgroups.

The health food industry grew at a 15 percent compounded growth ratefrom 1992 to 1998 driven primarily by the demographics of the babybowmen and the population's interest in a health-conscious lifestyle.The growth rate slowed substantially during 1999 and is expected to bearound 10 percent for the next three years. Various sources estimate1999 sales of domestic natural products at between $25 billion and $35billion.

Over the past several years, the increased popularity of alternativemedicine and the growing number of health conscious consumers havecontributed to increased sales of nutritional supplements. This trend isexpected to continue, with sales increasing further in the future. Thepublic awareness of the positive effects of vitamins and nutritionalsupplements on health has been heightened by widely publicized reportsof scientific findings supporting such claims. The non-elasticity ofdemand for natural food products has also underwritten the growth of theindustry. We observe that demand for health food products appears to beless price-sensitive than demand for regular foods. We believe Consumersare willing to pay premium prices for such products fin two importantreasons:

1. They believe in the health benefits of consuming such products

2. Their busy lifestyles demand the convenience of vitamins andnutritional supplements

Increasing numbers of health professionals recognize the benefits ofnutritional supplements and advocate their use in preventing illnessessuch as heart disease and strokes. Similarly, governments and healthcare providers looking to cut healthcare costs emphasize preventativehealthcare. Recent studies indicate a correlation bet the regularconsumption of selected nutritional supplements and reduced incidencesof a wide range of conditions such as cancer, heart disease, stroke, andarthritis.

The aging of the U.S. population and a corresponding shift toward focuson preventative health measures, prominently including good diet, willcontinue to increase demand for vitamins and nutritional supplements.According to the U.S. Census Bureau, the 36-and-older age group ofconsumers, which represents a substantial majority of regular users ofvitamins and nutritional supplements, is expected to grow significantlyfaster through year 2010 than the general population. Industry sourcesalso report that vitamin consumers are taking more vitamins andnutritional supplements per day than in the past. Consolidation, strongdemographic trends, and more science-based nutrition is expected in thecoming years.

Because of the foregoing reasons there is a desire in the field foralternate methods to deliver nutritional suipplements.

SUMMARY OF THE INVENTION

The present invention relates to various oral/buccal transmucosalsystems for delivering nutritional supplements to mammal and/or humanbodies.

Such oral/buccal transmucosal systems include quick dissolve strips,thin-film composites, powders, gels, sprays, time release lozenge orreservoir packets, and other oral/buccal transmucosal drug/substancedelivery systems.

One such oral/buccal transmucosal system that could be used to delivernutritional supplements is the 3M™ Cydot™ System offered in severalconfigurations including matrix and reservoir designs. Another suchoral/buccal transmucosal system that could be used to delivernutritional supplements is Zengen Inc.'s “oral strip bilayer system”which is being used in Chloraseptic Relief Strips™. Yet another systemcould be a “tea bag” device similar to a Skoal Bandit™ product.

Such nutritional supplements include but are not limited to Iron,Sodium, Calcium, Magnesium, Carbohydrates, Protiens, Sugars (Glucose),Zinc, Molybdenum, Copper, Potassium, Manganese, Chlorides, Bicarbonateand Carbonate, Aluminium, Arsenic, Bromine, Cadmium, Chromium, Chlorine,Cobalt, Fluorine, Iodine, Manganese, Molybdenum Nickel, Phosphorus,Selenium, Silicon, Vanadium, Zinc, Amino Acids, Vitamin A, Vitamin D,Vitamin E, Vitamin K, Vitamin C, Vitamin B complex, Thiamine (Vitamin31), Riboflavin (Vitamin 132). Niacin (Vitamin B3), Pyridoxine (VitaminB6), Biotin, Pantothenic Acid and Pantethine, Folic Acid, Vitamin B12,“Unofficial” B Vitamins including Choline and Inositol, Vitamin P(bioflavonoids), and/or other vital nutrients, in addition to varioushomeopathic/alternative substances.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

In order to fully understand the manner in which the above-reciteddetails and other advantages and objects according to the invention areobtained, a more detailed description of the invention will be renderedby reference to specific embodiments thereof.

Therapeutics can be effectively delivered across the mucous membrane.Transmucosal delivery is particularly attractive because these membranesare very thin and permeable. Such properties allow for the rapid uptakeof a drug (substance) into the body. This efficient uptake allows drug(substances) to bypass some of the body's natural defenses and enhancesthe effect of the therapeutic. Transmucosal delivery systems offerseveral benefits over other methods of delivery including:

Direct Absorption: Absorption through the mucous membrane leads directlyto the circulatory system. This allows drugs (substances) to bypass thegastrointestinal tract as well as first pass liver metabolism. This isimportant for biological therapeutics.

Rapid Onset: Drugs (substances) directly enter the circulatory system,which allows the therapeutic to be rapidly transported to the site ofneed. The faster the drug/substance reached its target area, the fasterit can begin to elicit its desired effect.

Lower Dosage: The avoidance of the gastrointestinal tract and first passmetabolism means that much less of the drug can be administered toachieve the same effect, allowing for lower dosages to be administeredand fewer side effects.

Transmucosal drug delivery is generally classified into three systems:

Nasal Transmucosal—Products in this category include nasal sprays,pumps, and gels. The majority of the drugs delivered to the nasalpassage are anti-inflammatories.

Oral/Buccal Transmucosals—These systems make use of saliva to releasethe therapeutic. Products include mucoadhesives, quick-dissolve stripsor other quick dissolve delivery systems, reservoir pouches or packets,and solid lozenge formulations.

Vaginal or Urethral Suppositories—Delivery systems in this category aredesignated to be absorbed directly by the vaginal or penile capillarybeds.

A viscous polysaccbaride matrix designed to trap foreign particles thatmay enter the system coats the mouth, nasal passage, vagina and urethra.This is a defense, which prevents damage to delicate tissues andcapillary beds which lie directly underneath the epithelium. Though themucous membrane protects the body from foreign matter and pathogens, thearea is much more permeable than mucous membrane. This permeabilityallows drugs delivered to the mucous membrane to quickly enter intocirculation.

Nutritional solutions may be used to orally replace nutrients lostduring vomiting, diarrhea, heavy perspiration, other forms of fluidloss, and/or other natural nutrient deficiencies related the body'sgenetic makeup or current genetic state, in addition to other causes ofnutrient deficiency.

Transmucosal Nutrient Supplements may be used in mild, moderate, and/orsever cases of nutrient loss.

Transmucosal delivery of nutrient supplements offer advantages over oraldelivery when negative issues relating to the gastrointestinal tract,the stomach, substance digestion and absorption, swallowing, protocolcompliance, and substance effectiveness as well as other issues withrespect to gastrointestinal metabolism are considered.

An appropriate edible film carrier for use with embodiments of thepresent invention can be selected by one of ordinary skill in the artdepending upon factors including the desired rate of dissolution,desired oral feel for the user, the compatibility of the thin filmcarrier and the active ingredients, production constraints, costs, orother factors. The film can also be thick or thin depending upon thesesame factors.

The desired rate for dissolution can vary depending of the specificapplication for the edible film. For example, for immediate delivery ofthe active ingredient, the film can be manufactured to rapidly dissolvein the oral cavity thus delivering the entire dosage of activeingredient at one time. The film can also be manufactured to dissolveover an extended period regulating the amount of active materialdelivered to the oral cavity over a desired length of time.

Specific film formulations and methods of manufacture are known in theart, for example see U.S. Pat. No. 5,948,430 to ZERBE et al.,incorporated herein by reference. Each film formulation usuallycomprises film formers, bulking agents, softeners, intense artificialsweeteners, sugar alcohol, natural sweeteners, flavors, cooling agents,surfactants, coloring agents, oils, and drying agents. These ingredientsare well known and widely available in the food industry.

The primary ingredient for an edible film according to the presentinvention is the film former, which in most cases can be any watersoluble film former. Film formers include but are not limited topullulan, guar gum, pectin, xanthan gum, alginates, gelatin, starches(including corn, potato, rice or tapioca), modified starches,matltodextrins, wheat gluten, carboxymethylcellulose, carrageenan konjacor locust bean gum.

An example of edible film according to the present invention isdescribed comprising a bi-layer film. The film consists of one watersoluble layer that serves as a substrate layer or active layer and asecond dry coat layer. The second dry coat layer settles into thesubstrate layer affixing itself to that bottom layer. While activeingredients may be contained in either layer, preferably the second drycoat layer will contain one or more active ingredients such as mentholor benzocaine or both. The dry coat layer is applied to the thin filmsurface after partial curing of the first (bottom) layer, affixingitself to this bottom layer. Said dry coat layer and similar layers areespecially effective with low dose active ingredients that require avery low moisture environment to remain stable. The second layer canalso contain substrates and partitioning agents.

The film is of a size such that it is fast dissolving. The weight perstrip may vary. Said weight of the strip may be in the ranges of about10 to 80 mg, about 20 to 70 mg, about 30 to 60 mg and about 50 mg. Themaximum dosing per strip may also vary depending on the choice of activeingredient. Said maximum dosing is preferably 12.5 mg. Activeingredients can be delivered in a solid or liquid format and dependingon dose levels, the Active ingredients can be oil or water soluble.Active ingredients that are stable in aqueous systems are preferred.Active ingredients that are not stable in an aqueous system, however,though not preferred, may still be used. Preferably, the dosage perserving is 1-2 strips but may vary depending on the size of theindividual strip and other factors known one skilled in the art.

Individual strips can be made in virtually any size, preferably thestrips are 13/16 inch by 1¼ inch rectangles. The thickness of the firstlayer is preferably in a range between about 0.040 to 1.1 micrometers.The thickness of the second dry coat layer is preferably in the range ofabout 0.007 to 0.02 micrometers. The thickness of the particularlylayers may be more or less than the values recited herein depending onfactors known to one skilled in the art such as load and processingchallenges.

Any standard manufacturing procedure known in the art may be used tomanufacture the film. An example of such a process can be found in U.S.Pat. No. 5,948,430 to ZERBE et al.

Further to the production method described in U.S. Pat. No. 5,948,430 toZERBE et al., the production of an edible film according to the presentinvention can also include an aeration step. This step includes aeratingthe mass prior to application onto a substrate. Aeration is mostpreferably achieved through mechanical agitation, mechanical reaction,or carbon dioxide aeration. The aeration step produces an edible filmhaving greater thickness and lower density than without aeration.

A further embodiment of the present invention includes an improved filmand method for making the same. The film can be used on living cells.Formation of the medicant-containing layer in the film does not requirea solvent and minimizes the likelihood of damage from heat and shear.The rate of dissolution or delivery of the medicant by the film can bereadily adjusted. The medicant-containing layer, while minimizing thelikelihood of heat induced medicant damage, permits heat to be utilizedto form a coating on the edible film. Hydrophilic components can bereadily incorporated in larger concentrations during production of themedicant-containing layer.

Further, the present invention includes an improved composition fordelivering a medicant in the oral cavity. The composition includes anapplied coating and a film layer.

The film layer is made from any polymer, softener, filler, matrix, orother composition. The film has an acceptable dissolution rate in theoral cavity for a particular thickness of film. For example, if the filmhas a thickness of 50 microns, it may be desirable for the film todissolve in the oral cavity within about fifteen seconds. Or it may bedesirable for the film to dissolve more slowly. By way of example, andnot limitation, the film can be made with pullulan, modified starch,pectin, carageenan, a maltrodextrin, or alginate.

The applied coating is a powder matrix including one or more medicants.The medicant can be contained in a powder carrier, or can itself be apowder. One advantage of the powder matrix is that it ordinarily doesnot require the use of a solvent. Another advantage of the powder matrixis that it ordinarily can, if desired, include in addition to themedicant a variety of different auxiliary compositions. A furtheradvantage of the powder matrix is that it can be admixed in a fluidizedbed that minimizes the generation of shear and heat. In a fluidized beddry air or another gas is dispersed upwardly through a plurality ofopenings to suspend and intermix particulate. Any desired means can beused to admix powders. Another advantage of mixing or suspending powderin a fluidized bed is that the dry air suspending the powder particlestends to prevent agglomeration of the particles. The admixed powdermatrix can also be stored (i.e., suspended) in the fluidized bed, priorto the application of the admixed powder matrix to the film layer. Thepowder matrix can be applied in any desired manner, including sifting,screening, atomization, static, mechanical agitation, etc. For example,the powder matrix can be atomized through a Nordson or similar staticspray gun using compressed air. One such gun creates a fine mist sprayof powder particles. The gun statically electrically charges the powderparticles so they adhere to a surface of the film layer that isreceiving the powder particles. Another process for applying the powderparticles is to admix the particles with a liquid carrier to form aparticle—liquid solution. The particle—liquid solution is sprayed on thefilm layer. The liquid carrier evaporates, leaving the powder particleson the film. The liquid carrier preferably does not cause the powderparticles to dissolve in the liquid carrier.

One auxiliary composition that can be included in the powder matrix withthe medicant is a composition that dissolves slowly over a selectedperiod of time. Such an auxiliary dissolution control composition can beutilized to slow the release of medicant in the oral cavity. Examples ofthis kind of auxiliary composition are, without limitation, gel formingcompositions like carrageenan, gelatin, alignates, pullulan, PVP, andother hydrophilic materials; cyclodextrin; and, inert materials likecalcium and fibers. For example, the fibers can comprisecarboxymethylcellulose.

Another auxiliary composition the can be included in the powder matrixwith the medicant is an absorption composition that absorbs water orsaliva. Such an auxiliary absorption composition can be also be used toslow the release of medicant, and/or, to form a gel. The gel can, ifdesired, cause the strip to become chewable, similar to a very softjelly-bean. As used herein, an auxiliary composition is termed a gel if,when it is placed in the oral cavity or in contact with another sourceof bodily liquid, (1) the auxiliary composition absorbs at least fourtimes it weight of water or of saliva or other aqueous solution in aselected period of time, or (2) the auxiliary composition swells to atleast three times its thickness in a selected period of time. Theselected period of time can vary but preferably is from five seconds tofifteen minutes, most preferably five seconds to five minutes. Examplesof gel auxiliary compositions include, without limitation,carboxymethylcellulose, pectin, modified starches, gelatin, andcarrageenan. These compositions can be used alone or in combination. Oneadvantage of a gel is that it tends to slow the dissolution of themedicant and to maintain the medicant in the oral cavity for a longerperiod of time.

A further auxiliary composition that can be included in the powdermatrix is a composition that, when placed in the oral cavity in contactwith the mucosa therein, adheres to the mucosa. The concentration ofsuch auxiliary adhesion compositions in the powder matrix can beadjusted to vary the length of time that the film adheres to the mucosaor to vary the adhesive forces generated between the film and mucosa.The auxiliary adhesion compositions adhere to the oral mucosa or tomucosa or tissue in other parts of the body, including the mouth, nose,eyes, vagina, and rectum. Examples of auxiliary adhesion compositionsinclude carboxymethycellulose, polyvinyl alcohol, polyvinyl pyrrolidone(povidone), sodiumalginate, methyl cellulose, hydroxyl propyl cellulose,hydroxypropylmethyl cellulose, polyethylene glycols, carbopol,polycarbophil, carboxyvinyl copolymers, propylene glycol alginate,alginic acid, methyl methacrylate copolymers, tragacanth gum, guar gum,karaya gum, ethylene vinyl cetate, dimenthylpolysiloxanes,polyoxyalkylene block copolymers, and hydroxyethylmethacrylatecopolymers. All examples of composition provided herein are givenwithout limiting the use or inclusion of other comparable orfunctionally equivalent compositions even though such comparable orfunctionally equivalent compositions are not listed.

Still another auxiliary composition that can be included in the powdermatrix is a flow composition that, when subjected to a curing process,flows to form a smoother or shinier coating on the exterior of the filmlayer. One preferred curing process is heating the film layer withpowder coating to a selected temperature above 76 degrees F. to causethe auxiliary flow composition to soften and flow. Examples of this kindof auxiliary composition are lipids (including various animal andvegetable fats) waxes, particularly low melting point waxes, andpolyols, particularly low melting point polyols that can be admixed inpowder form or than can included be in powder particles containing amedicant or other compositions. The medicant itself, may also have theproperty of flowing at an elevated temperature in excess of 76 degreesF. to form a smoother or shinier coating.

Other auxiliary compositions that can be included in the powder matrixinclude, without limitation, bulking agents, fillers, pigments(coloring), flavorings, and sweeteners.

Combinations of auxiliary compositions can be included in the powdermatrix to achieve a desired function. For example, if it is desired toslow the dissolution of a medicant, less soluble fillers and fibers canbe included in the powder matrix along with a high concentration ofpolymers that have a very high degree of ability to adhere to the oralmucosa lining the mouth.

The powder matrix is normally administered to the film layer to form theapplied coating after the film layer has been manufactured.

The dry powder matrix will normally contain a minor amount of retainedor bound water or other liquid, typically less than about ten percent byweight. The level of moisture in the powder matrix normally should notcause the powder particles to stick or adhere to one another duringintermixing of powders to form the powder matrix and during applicationof the powder matrix to the film layer.

By way of example, and not limitation, the film layer can be producedusing a highly water-soluble polymer comprising a natural or syntheticwater-soluble polymer. The polymer preferably has good film moldability,produces a soft flexible film, and is safe for human consumption. Onesuch polymer can be a water-soluble cellulose derivative likehydroxypropyl cellulose (HPC), methyl cellulose, hydroxypropylalkylcellulose, carboxymethyl cellulose or the salt of carboxymethylcellulose. Or, the polymer can comprise an acrylic acid copolymer or itssodium, potassium or ammonium salt. The acrylic acid copolymer or itssalt can be combined with methacrylic acid, styrene or vinyl type ofether as a comonomer, poly vinyl alcohol, poly vinyl pyrrolidone,polyalkylene blycol, hydroxy propyl starch, alginic acid or its salt,poly-saccharide or its derivatives such as trangacanth, bum gelatin,collagen, denatured gelatin, and collagen treated with succinic acid oranhydrous phthalic acid. By way of example, the following can beincluded in the powder matrix as adhesives: poorly water-solublecellulose derivatives including ethyl cellulose, cellulose acetate andbutyl cellulose; shellac; higher fatty acids including steric acid andpalmitic acid. The following can also, without limitation, be used toproduce the film layer: pullulan, maltodextrin, pectin, alginates,carrageenan, guar gum, other gelatins, etc.

Bulking agents that can be included in the powder matrix include, by wayof example and not limitation, avicel, sugar alchohols including manitoland sorbitol and xylitol and isomalt, lactic sugar, sorbitol dextrin,starch, anhydrous calcium phosphate, calcium carbonate, magnesiumtrisilicate, silica, and amylase.

The size of particulate in the powder matrix can vary as desired, but ispreferably in the range of 10 mesh to 400 mesh or finer, preferably 40mesh to 300 mesh.

The thickness of the film layer can vary as desired, but typically is inthe range of 0.01 mm to 3.00 mm, preferably 0.03 mm to 1.00 mm.

The powder matrix can be applied to one or both sides of the film layer.The film layer includes upper outer surface on the top of the film layerand includes a lower outer surface on the bottom of the film. The upperouter surface is generally parallel to the lower outer surface. The topof the film is generally parallel to the bottom of the film. Thethickness of the powder matrix layer can vary as desired, but ispreferably in the range of 0.001 mm to 3.00 mm, preferably 0.01 mm to1.00 mm.

If desired, after the powder matrix layer is applied to the film layer,an additional layer or layers can be applied over the powder matrixlayer to seal the powder matrix layer, slow the dissolution of themedicant from the powder matrix layer, etc.

If desired, multiple powder matrix layers can be applied to the filmlayer. The film layer can comprise a laminate of two or more layers.Methods for producing the film layer and incorporating plasticizers,bulking agents, taste modifying agents, pigments, etc. in the film layerare well known in the art and not described in detail herein. Since themedicant is being applied to the film layer in a dry powder form, thelikelihood of adverse interactions between the medicant and compositionscomprising the film layer is lessened.

Unless otherwise specified or required by the context, the term edibleas used herein is used interchangeably with the term orally consumable,and generally means that the article may be placed in the mouth, oralcavity, on the tongue, or the like, without significant detrimentaleffect to the recipient.

In certain embodiments the compositions and films of the presentinvention may contain at least one flavoring and/or odorant compositionthat renders the composition or film palatable. Any effective flavor orodor may be used. The flavoring or odor agent or agents are present inany effective amount, including, for example, in an amount ranging fromabout 0.5 to 40 wt. %, 1 to 30 wt. %, 5 to 15 wt. %, 0.5 to 15 wt. %.The flavorings may be natural or artificial, or combinations thereof.

Unless otherwise specified or required by the context, the edible filmsof the present invention may be manufactured in any effective manner.U.S. Patent Application Nos. 20010022964, 20020131990 and 20020019447and U.S. Pat. Nos. 6,419,903, 3,931,146, 5,411,945, 6,010,716,5,629,003, 5,948,430, 6,177,096, 6,284,264, 5,700,478, 6,449,925,4,072,551, 4,083,741, all of which are incorporated herein by referenceas if fully set forth herein, describe methods for making edible films.These, and other methods known in the art, or described herein, may beused in accordance with the present invention.

EXAMPLES Example Application 1 Nutrient Deficiency Through ExcessiveFluid Loss

Nutrient loss thorough diarrhea and vomiting in particular can cause asevere condition, especially in infants and young children, and mayresult in death. Diarrhea frequently involves colonization of the smallintestine with enteropathogenic strains of E. Coli which produce heatstable and/or heat labile enterotoxins. Related enterotoxins areproduced by other enteropthogens such as cholera, and also causediarrhea. These enterotoxins stimulate fluid secretion in the gut lumenand cause diarrhea. Associated fluid loss may lead to death.

In cases of severe dehydration corrective parenteral (intravenous)therapy is often necessary. In cases of mild to moderate dehydration,oral rehydration solutions provide a safe and economical alternative tointravenous therapy. Oral electrolyte solutions used in oral maintenanceor rehydration therapy consist of a mixture of electrolytes and acarbohydrate component such as glucose or dextrose.

Transmucosal Nutritional Supplements may be used in mild, moderate,and/or sewer cases of nutrient loss through diarrhea and vomiting.

Example Application 2 Nutrient Deficiency in the Aging Population

Between 50% and 75% of America's 3 million nursing borne residents havesome difficulty in swallowing. In one Canadian nursing home study of 349patients, 68% exhibited signs of dysphagia, and 40% exhibitedchallenging behaviors when asked to swallow medication.

Dosing these millions of patients presents a great challenge to nursinghomes, menial institutions, and even general hospitals.

A study by the Department of Health & Human Services reported toCongress on Feb. 17, 2002 found that more than 90% of nursing homes areundenauffed, and would have to spend an unbudgeted $7.8 billion a yearto meet even marginal care standards. Patients with chronic diseasessuffer the most because of inadequate medication-administration support.

In both home care and nursing homes, the psychiatric effects of agingfrequently complicate administration of solid dosage forms. Prevalenceof agitation in the nursing home environment ranges from 75% to 90%;incidence of psychosis in patients with Alzheiiner's disease is 20% atthe one-year benchmark and 50% at three years. The hassle of attemptingto medicate these patients at home with oral solid dosage forms leads tocaregiver burnout, and eventually, institutionalization of the patient.Typical of the disorders that involve underappreciated swallowingdifficulties.

Parkinson's disease: One of the mast visible symptoms of Parkinson'sdisease is drooling, which affects 80% to 90% of patients. Droolingresults from an inability to swallow saliva, not overproduction—in fact,Parkinson's disease patients actually produce less saliva than normalpeople. Anticholinergic drugs commonly prescribed to “dry up” excesssaliva actually results in sticky saliva that is even more difficult toswallow.

Other patients with chronic swallowing difficulties include those withchronic obstructive lung disease, stroke, and Alzheimer's disease, andthose with diseases and radiation therapy to the head and neck.

Still another reason for considering transmucosal drug delivery may bethe reduction or elimination of hepatic metabolism. The liversignificantly alters some drugs, like hormones. For others, first-passhepatic metabolism may impair the metabolism of other drugs with whichthe patient is being treated.

Early testing of oral drugs in healthy volunteers can mask difficultiesin dosage once actual patients are being treated. It is one thing toproduce pharmacokinetic curves for an oral 5-HT3 antagonist in normalvolunteers—it may be quite another to use those curves to predict howmuch drug was absorbed by a patient who vomited due to chemotherapy,shortly after taking a capsule.

Finally, some medications, when delivered as oral solid dosage firms,expose the entire body or specific organs to unacceptable drug levels,at least for some patients. Examples of those drugs include the NSAIDs,erectile-dysfunction treatments, and antifungals.

In the case of NSAIDs, systemic administration of oral solid dosageforms, usually to treat a highly localized pain, results in blood levelsthat induce GI bleeding responsible for approximately 76,000hospitalizations and 7,600 deaths annually.

Accordingly, Transmucosal Nutritional Supplements may be of benefit incases such as the elderly, infants, and other situations in which oraldelivery may not be the preferred option.

Example Application 3 Nutrient Deficiency and Hyponatremia (Low BloodSodium)

In September 1999, a 19-year-old U.S. Air Force recruit collapsed duringa 5.8-mile walk, with a body temperature of 108 degrees Fahrenheit.Doctors concluded he had died of both heat stroke and low blood sodiumlevels as a result of overhydration.

During January 2000, a 20-year-old trainee in the U.S. Army drank around12 quarts of water during a 2- to 4-hour period while trying to producea urine specimen for a drug test. She then experienced fecalincontinence, lost consciousness and became confused, then died fromswelling in the brain and lungs as a result of low blood sodium.

In March 2001, a 19-year-old U Marine died from drinking too much waterafter a 26-mile march, during which he carried a pack and gear weighingmare than 90 pounds. Although he appeared fine during the beginningstages of the 8-hour walk, towards the end he began vomiting andappeared overly tired. He was then sent to the hospital, where he fellinto a coma, developed brain swelling and died the next day. It isunclear how much water he drank during the march, but Marines were givena “constant emphasis” on drinking water before and during the activity,Gardner writes in the latest issue of Military Medicine.

Accordingly, Transmucosal Nutritional Supplements (sodium supplements)may be of benefit in preventing Hypoatremia.

Example Application 4 Iron Deficiency

Anemia is a condition where red blood cells are not providing adequateoxygen to body tissues. There are many types and causes anemia. Irondeficiency anemia is a decrease in the number of red cells in the bloodcaused by too little iron.

Iron deficiency anemia is the most common form of anemia. Approximately20% of women, 50% of pregnant women, and 3% of men are iron deficient.Iron is an essential component of hemoglobin, the oxygen-carryingpigment in the blood. Iron is normally obtained though the food in thediet and by recycling iron from old red blood cells. Without it, theblood cannot carry oxygen effectively and oxygen is needed for thenormal functioning of every cell in the body.

The causes of iron deficiency are too little iron in the diet, poorabsorption of iron by the body, and loss of blood (including from heavymenstrual bleeding). It can also be related to lead poisoning inchildren.

Anemia develops slowly after the normal stores of iron have beendepleted in the body and in the bone marrow. Women, in general, havesmaller stores of iron than men and have increased loss throughmenstruation, placing them at higher risk for anemia than men.

In men and postmenopausal women, anemia is usually caused bygastrointestinal blood loss associated with ulcers the use of aspirin ornonsteroidal anti-inflammatory medications (NSAJDS), or certain types ofcancer (esophagus, stomach, colon).

High-risk groups include women of child-bearing age who have blood lossthrough menstruation; pregnant or lactating women who have an increasedrequirement for iron; infants, children, and adolescents in rapid growthphases, and people with a poor dietary intake of iron. Risk factorsrelated to blood loss are peptic ulcer disease, long term aspirin useand colon cancer.

The cause of the deficiency must be identified, particularly in olderpatients who are most susceptible to intestinal cancer.

Oral iron supplements are available (ferrous sulfate). The bestabsorption of iron is on an empty stomach, but many people are unable totolerate this and may need to take it with food. Milk and antacids mayinterfere with absorption of iron and should not be taken at the sametime as iron supplements. Vitamin C can increase absorption and isessential in the production of hemoglobin.

Supplemental iron is needed during pregnancy and lactation becausenormal dietary intake rarely supplies the required amount.

The hematocrit should return to normal after 2 months of iron therapy,but the iron should be continued for another 6 to 12 months to replenishthe body's iron stores, which are contained mostly in the bone marrow.

Intravenous or intra-muscular iron is available for patients who can'ttolerate oral forms.

Iron-rich foods include raisins, meats (liver is the highest source),fish, poultry, eggs (yolk), legumes (peas and beans), and whole grainbread.

Accordingly, Transmucosal Nutritional Supplements (iron supplements) maybe of benefit as a source of iron, and in the prevention of irondeficiency/anemia

Example Application 5 Calcium Deficiency

Calcium is essential for many body functions, including regulation ofthe heartbeat, conduction of nerve impulses, stimulation of hormonesecretions and clotting of blood, as well as for building andmaintaining a healthy skeleton.

Calcium is a mineral found in many foods and adequate calcium intake isimportant because the human body cannot produce calcium. Even afterreaching full skeletal growth, adequate calcium intake is importantbecause the body loses calcium every day through shed mucous membrane,nails, hair, and sweat as well as through urine and frees. This lostcalcium must be replaced daily through the diet. When the diet does notcontain enough calcium to perform these activities, calcium is takenfrom the bones, the storage area for calcium.

The National Academy of Sciences and the National OsteoporosisFoundation recommend daily calcium intakes of 1000-1200 mg/day for adultmen and women. According to experts, food is the best source of calcium;however, most Americans do riot have enough calcium in their diets.Fortunately, calcium-fortified foods and calcium supplements can fillthe gap, ensuring that the daily calcium requirement is met. The amountneeded from a supplement depends on how much calcium is consumed fromfood sources.

Calcium exists in nature only in combination with other substancescalled compounds. Several different calcium compounds are used insupplements including calcium carbonate, calcium phosphate and calciumcitrate. These compounds contain different amounts of elemental calcium,which is the actual amount of calcium in the supplement. It is importantto read the label carefully to determine how much elemental calcium isin the supplement and how many doses or pills to take.

Calcium supplements are available without a prescription in a wide rangeof preparations and strengths, which can make selecting one a confusingexperience. Many people ask which calcium supplement they should take;the “best” supplement is the one that meets an individual's needs basedon tolerance, convenience, cost and availability. In choosing a calciumsupplement, the following are important considerations:

Purity—Choose calcium supplements that are known brand names with provenreliability. Look for labels that state “purified” or have the USP(United States Pharmacopeia) symbol. Since applying for the USP symbolis voluntary, however, many fine products may not display this symbol.Avoid calcium from unrefined oyster shell, bone meal or dolomite withoutthe USP, as these historically have contained higher lead levels orother toxic metals.

Absorbability—Most brand name calcium products are absorbed easily inthe body. If the product information does not state that it isabsorbable, how well a tablet dissolves can be determined by placing itin a small a of warm water for 30 minutes, stirring it occasionally. Ifhasn't dissolved within this time it probably will not dissolve in thestomach. Chewable and liquid calcium supplements dissolve well becausethey are broken down before they enter the stomach. Calcium, whetherfrom the diet or supplements, is absorbed best by the body when it istaken several times a day in amounts of 500 mg or less, but taking itall at once is better than not taking it at all. Calcium carbonate isabsorbed best when taken with food. Calcium citrate can be takenanytime.

Tolerance—While calcium supplements generally are a satisfactory optionfor many people, certain preparations may cause side effects, such asgas or constipation, in some individuals. If simple measures such asincreased fluids and fiber intake do not solve the problem, another formof calcium should be tried. Also, it is important to increase supplementintake gradually; take 500 mg a day for a week, then add more calciumslowly.

Calcium Interactions—It is important to talk with a physician orpharmacist about possible interactions between prescription orover-the-counter medications and calcium supplements. For example,calcium supplements also may reduce the absorption of the antibiotictetracycline. Calcium also interferes with iron absorption, so a calciumsupplement should not be taken at the same time as an iron supplement.The exception to this is when the iron supplement is taken with vitaminC or calcium citrate. Any medication to be taken on an empty stomachshould not be taken with calcium supplements.

Combination Products—Calcium supplements are available in a dazzlingarray of combinations with vitamins and other minerals. While vitamin Dis necessary for the absorption of calcium, it is not necessary that itbe in the calcium supplement (see winter 1998 issue of OsteoporosisReport for information on vitamin D). Minerals such as magnesium andphosphorus also are important, but usually are obtained through food ormultivitamins. Most experts recommend that nutrients come from abalanced diet, with multivitamins used to supplement dietarydeficiencies.

Most published studies show that low calcium intake is associated withlow bone mass, rapid bone loss and high fracture rates. Adequate calciumintake will help ensure that calcium deficiency is not contributing to aweakening of the skeleton; however, this is only one of the stepsnecessary for bone health. A high calcium intake will not protect aperson against bone loss caused by estrogen deficiency, physicalinactivity, smoking, alcohol abuse or various medical disorders ortreatments.

Accordingly, Transmucosal Nutritional Supplements (calcium supplements)may be of benefit as a source of calcium, and in the prevention ofcalcium deficiency.

Example Application 6 Micronutrient Influence Upon Muscle Contractions(Muscle Cramps)

Muscle cramps are sudden electrically active contractions elicited bymotor neuron hyperexcitement, or the inability of the myosin head torelease from its attraction to the actin head protein. Some have assumedthat exertional cramping may be the result of fluid electrolyteimproprieties. Modem research science is divided on the importance ofsweat losses of sodium, chloride, potassium, and magnesium and regardsthem as trivial, therefore not evidential as a primary cause of the“Rigor Complex”. There is, however, some preliminary evidence whichindicates that ATP translocation is associated with sodium, potassium,-ATP-ase. Balance of fluid ratio and electrolyte intracellular toextracellular levels in the presence of Adenosine Triphosphate and itsAdenosine Triphosphatase enzyme would appear mandatory for optimummuscle function. A nationally ranked tennis player has experiencedunexplainable muscle heat cramps during play. Medical examinations andhistory were unremarkable, and were confirmed by in-patient blood serumprofiles. On court evaluation of sweat loss composition and a 3-daydietary analysis revealed that sodium loss during play far exceededdietary intake. Increase of daily dietary sodium chloride eliminatedheat cramps reoccurrence.

Among the elderly, frequent cramping caused by compromised circulationmay provide a model for the extreme, but similar physiologicalenvironment experience by an athlete during heat stress. Idiopathiccramping among older people was found to be directly related toelectrolyte deficiencies, heat stress, metabolic myopathies, thyroiddisease, dystonias, reaction to medications, and hemodialysis. It issuggested that treatment include stretching, oral Vitamin E, and/orQuinine Sulfate supplements. Further, no single treatment results in oneeffective remedy.

Dr. T. D. Noakes (1991) summarizes exertional cramps as follows: (1)Exhaustion related to glycogen depletion for fresh ATP replenishment,(2) Excessive fluid volume to electrolyte profile. He suggests intake of16 ounces fluid using 60-120 grams carbohydrates prior to and duringeach how of prolonged endurance training.

CALCIUM: IONIZED MINERAL OF INTEREST—During extraordinary muscle energymetabolism, mineral flux may deplete or vary normal electrolytehomeostatic ratios. Calcium is the most abundant mineral and the fifthmost abundant element found in the human body. It is therefore vital tomuscle contraction, nerve transmission, blood clotting, and a multipleof metabolic functions. Bones act as a calcium reservoir, providing itwhen blood serum values decline below 10 mg/100 ml, regulated byparathyroid hormonal controls. Over half of the serum calcium isionized, while the remainder is protein-bound or associated with organicand inorganic acids. Protein-bound calcium acts as a weak electrolyte,while metabolically active ionized calcium is used by the blood andserum for muscle contraction.

During exercise blood calcium falls, arousing the parathyroid gland tostimulate vitamin D activation of ionized calcium release from bonestores. As calcium levels are reinstated, parathyroid stimulation halts,and calcitonin from the thyroid is released, thereby halting boneresorption/release. (Garrison & Somer 1995) Calcium depletion sensitizesneural muscle tetany. Calcium is vital to synaptic release ofneurotransmitter substances which enable nerves to excite and relaxduring muscle contractions. The volume of neurotransmitter release isproportionate to ionized calcium concentration in the terminal membrane,and inversely proportionate to magnesium concentration. Serotonin,Acetylcholine, and Norephinephrine transmitter levels are affected bythe enzymatic influences of both calcium and magnesium upon striated andsmooth muscle contraction. Without substantial amounts of calcium, theglycogen enzyme, phosphorylase kinase is not able to breakdown glycogento glucose-6-P for energy metabolisms. Calcium also activates theadenosine triphosphatase enzyme for the hydrolysis of ATP. Dr. Balch(1990) stated that muscle cramps are “Commonly caused by acalcium-magnesium imbalance and/or vitamin E deficiency.” He recommendsa daily dietary or supplemental intake of 2:1 Calcium (1500 mg.) toMagnesium (750 mg.) and 400-1000 IU of vitamin E for prevention ofmuscle cramps. Substantial research noted leg cramps during pregnancywere caused by alterations of calcium metabolism. (Pitikin 1983) Studiesby Hammar (1987), Knowles (1981), Odendahl (1974), and Page (1953)further suggest that supplementation of calcium or reduction ofphosphorus may prevent and relieve such cramping in the legs. Possiblyrelated to calcium balance, reduced serum magnesium has been associatedwith tetany and muscle cramping. Similar findings have confirmedevidence when supplemental ingestion of calcium and magnesium relievedtetanical symptoms.

ELECTROLYTE BALANCE: DELICATE AND DELIBERATE—The Cations and Anions offluid electrolyte composition are never static, but are proportionatelybalanced within the compensatory rates of metobalic activity bothintracellularly and extracellularly. Pivotal losses of calcium andmagnesium from muscle exhaustion, fluid dehydration from sweat loss,depletion of extracellular cation stores of sodium or intracellularcation stores of potassium are significant factors staged for musclefailure, i.e., a cramp event. While the previously mentioned case studyof a nationally-ranked tennis player whose severe exertional musclecramps were solved by dietary sodium supplementation, modern scienceconsiders one solution insignificant in terms of scientific methodologyfor settling on conclusive evidence. Muscle cramps have been associated‘with a hypokalemic tissue environment, and were readily relieved bypotassium supplements. (Portier 1973) Glatzel (1980) was successfullytreating nocturnal cramps with dietary sodium chloride. Strong evidenceexists for the role of electrolyte depletion associated with musclespasms, cramps, and seizures, but inconclusive from present researchliterature. In fact, depletion of muscle glycogen, fluid overhydration,and the lack of vitamin substrates with enzymatic influence en fuelselection are also presently considered suspects.

VITAMINS NECESSARY FOR FUEL CONVERSION AND FREE RADICAL SCAVENGING:VITAMIN 8-6, VITAMIN E—Vitamin E supplementation to shown to relievemuscle tramping in several clinical observations by Lotzof (1977) andCathcart (1972). Two separate experimental studies by Ayres (1969 &1974) confirmed the findings of Catheart amd. Lotzof. Dr. Balch'sresearch of the literature (1990) recently was added to theaforementioned scholarship. Nocturnal muscle spasms anddistal/peripheral small muscle cramps were releived by oral ingestion ofvitamin B-6 (Pyrodoxine) in the studies performed by Ellis and Presley(1973)

Accordingly, Transmucosal Nutritional Supplements may be of benefit inalleviating or extending the onset of muscle contractions.

Example Application 7 Oral/Buccal Transmucosal Nutrient Delivery as anAthletic Supplement to Combat Nutrients Lost Through Excessive FluidLoss

Another aspect of the present invention relates to transmucosal methodsand products for replenishing nutrients and supplying additionalcomponents to a subject involved in strenuous exercise, includingeletrolytes, which avoids many of the limitations associated with sportsdrinks or other orally ingested nutritional supplements.

The invention in one aspect is a quick-dissolve strip (or reservoirpouch/packet) for administering nutrients utilized during exercise andother periods of high energy exertion.

The nutrients are delivered from the quick strip directly to the bloodstream where they can supply the necessary energy or maintenance ofhomeostatic conditions in the body. There is no need for the nutrientsto pass through the gastrointestinal tract where absorption would be alimiting factor.

The delivery of an athletic supplement using a quick-dissolve stripoffers several advantages over traditional delivery methods. Forinstance, the quick-dissolve strip avoids gastrointestinal metabolism ofthe athletic supplement, reduces first pass effects and may if desirableprovide a longer course of release of the components of the athleticsupplement than traditional methods such as the use of sports drinks orother orally ingested nutritional supplements.

The quick-dissolve strip may include many different concentrations ofthe components of the athletic supplement.

The quick-dissolve strip may be any type of conventional quick-dissolvestrip, such as a transmucosal quick-dissolve strip, a sublingualquick-dissolve strip, or a buccal quick-dissolve strip. In a preferredembodiment the quick-dissolve strip includes a permeation enhancingamount of at least one mucous membrane permeation enhancer.

The transmucal quickdissolve strip may be of any shape, such as oblong,square, round, rectangular, etc. The transmucosal quick-dissolve stripmay also have a variety of sizes.

The quick-dissolve strip of the present embodiment provides all of thenutritional, carbohydrate, and energy requirements of an athlete underconditions of physical stress without causing gastrointestinaldisturbances.

Accordibngly, Transmucosal Nutritional Supplements (electrolyte/othersupplements) may be of benefit to replace nutrients lost throughexcessive fluid loss from physical activities.

Example Appication 8 Tranmucosal Nutrient Product Mix (Composition)

The following is a formulation for a Transmucosal Nutrient Supplementcomposition (for excessive body fluid loss)

1 part Potassium Chloride

1.93 parts Trisodium Citrate

2.33 parts Sodium Chloride

13.33 parts Glucose

Said formualtion is to be combined with proper fluid (water) rehydrationguidelines.

Example Application 9 Vitamin Deficiencies, Micronutrient Deficiencies

Dietary deficiencies of vitamins and minerals—life-sustaining nutrientsneeded only in small quantities (hence. “micronutrients”)—cause learningdisabilities, mental retardation, poor health, tow work capacity,blindness, and premature death. The result is a devastating publichealth problem: about 1 billion people, almost all in developingcountries, are suffering the effects of these dietary deficiencies, andanother billion are at risk of falling prey to them.

To grasp the enormous implications at the country level, consider acountry of 50 million people with the levels of micronutrientdeficiencies that exist today in South Asia. Such a country would sufferthe following losses each year because of these deficiencies:

20,000 deaths

11,000 children born cretins or blinded as preschoolers

1.3 million person-years of work lost due to lethargy or more severedisability

360,000 student-years wasted (3 percent of total student body)

In terms of losses by type of deficiency, more than 13 million peoplesuffer night blindness or total blindness from the lac of vitamin A. Inareas without adequate iodine in the diet, five to ten offspring ofevery 1,000 pregnant women are dead upon birth or soon thereafter due toiodine deficiency. Severe iron deficiency causes as many as one in fivematernal deaths, as well as the death of about 30 percent of childrenwho enter the hospital with it and do not get a blood trransfusion(those who do get the transfusion are exposed to other risks).

Accordingly, Transmucosal Nutritional Supplements (micronutrientsupplements) may be of benefit for vitamin/micronutrient deficienciesworldwide.

While the invention is described in terms of a specific embodiment,other embodiments could readily be adapted by one skilled in the art.Accordingly, the scope of the present invention is limited only by thefollowing claims.

1. A composition comprising: a film layer; a coating, wherein thecoating is applied to at least one side of the film layer; and anutritional supplement.
 2. The composition of claim 1 wherein thecoating comprises a powder matrix.
 3. The composition of claim 1 whereinthe film layer comprises the nutritional supplement.
 4. The compositionof claim 2 wherein the powder matrix comprises the nutritionalsupplement.
 5. The composition of claim 4 wherein the nutritionalsupplement is selected from the group consisting of Iron, Sodium,Calcium, Magnesium, Carbohydrates, Proteins, Zinc, Molybdenum, Copper,Potassium, Manganese, Chlorides, Bicarbonate and Carbonate, Aluminium,Arsenic, Bromine, Cadmium, Chromium, Chlorine, Cobalt, Fluorine, Iodine,Manganese, Molybdenum Nickel, Phosphorus, Selenium, Silicon, Vanadium,Amino Acids, Vitamin A, Vitamin D, Vitamin E, Vitamin K, Vitamin C,Vitamin B complex, Thiamine (Vitamin 31), Riboflavin (Vitamin 132).Niacin (Vitamin B3), Pyridoxine (Vitamin B6), Biotin, Pantothenic Acidand Pantethine, Folic Acid, Vitamin B12, “Unofficial” B Vitaminsincluding Choline and Inositol, Vitamin P (bioflavonoids).
 6. Thecomposition of claim 4 wherein the nutritional supplement comprises anelectrolyte.
 7. The composition of claim 4 wherein the nutritionalsupplement comprises a vitamin.
 8. The composition of claim 6 whereinthe powder matrix comprises an auxiliary dissolution controlcomposition.
 9. The composition of claim 8 wherein the auxiliarydissolution control composition comprises one or more of carrageenan,gelatin alginates, pullulan, PVP, cyclodextrin, calcium, or fibers. 10.The composition of claim 6 wherein the powder matrix comprises anabsorption composition.
 11. The composition of claim 10 wherein theabsorption composition comprises one or more of carboxymethylcellulose,pectin, modified starches, gelatin, or carrageenan.
 12. The compositionof claim 6 wherein the powder matrix comprises an adhesive.
 13. Thecomposition of claim 12 wherein the adhesive comprises one or more ofpoorly water soluble cellulose derivatives including ethyl cellulose,cellulose acetate and butyl cellulose, shellac, or fatty acids includingsteric acid and palmitic acid.
 14. The composition of claim 6 whereinthe powder matrix further comprises a mucosa adherent.
 15. Thecomposition of claim 14 wherein the mucosal adherent is selected fromone or more of carboxymethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, sodiumalginate, methylcellulose, hydroxyl propyl cellulose,hydroxypropylmethyl cellulose, polyethylene glycols, carbopol,polycarbophil, carboxyvinyl copolymers, propylene glycol alginate,alginic acid, methyl methacrylate copolymers, tragacanth gum, guar gum,karaya gum, ethylene vinyl cetate, dimenthylpolysiloxanes,polyoxyalkylene block copolymers or hydroxyethylmethacrylate copolymers.16. The composition of claim 6 wherein the powder matrix comprises aflow agent.
 17. The composition of claim 16 wherein the flow agent is alipid, wax or polyol.
 18. The composition of claim 6 wherein the powdermatrix comprises a bulking agent.
 19. The composition of claim 19wherein the bulking agent comprises one or more of avicel, sugaralcohols including manitol, sorbitol, xylitol and isomalt, lactic sugar,sorbitol dextrin, starch, anhydrous calcium phosphate, calciumcarbonate, magnesium trisilicate, silica or amylase.
 20. The compositionof claim 6 wherein the powder matrix further comprises one or more of abulking agent, filler, pigment, flavoring agent, or sweetener.
 21. Thecomposition of claim 6 wherein the powder matrix comprises less thanabout 10% water by weight.
 22. The composition of claim 6 wherein thethickness of the film layer is in the range of about 0.01 mm to about 3mm.
 23. The composition of claim 6 wherein the thickness of the filmlayer is in the range of about 0.03 mm to about 1 mm.
 24. Thecomposition of claim 6 wherein the film layer comprises at least twolayers.
 25. A composition comprising: a film layer wherein the filmlayer rapidly dissolves in an oral cavity; and a powder coatingcomprising a nutritional supplement wherein the powder coating isapplied to at least one side of the film layer.
 26. The composition ofclaim 25 wherein the film layer dissolves within thirty seconds of beingplaced in the oral cavity.
 27. The composition of claim 25 wherein thefilm layer dissolves within 15 seconds of being placed in the oralcavity.
 28. The composition of claim 25 wherein the nutritionalsupplement is selected from the group consisting of Iron, Sodium,Calcium, Magnesium, Carbohydrates, Proteins, Molybdenum, Copper,Potassium, Manganese, Chlorides, Bicarbonate and Carbonate, Aluminium,Arsenic, Bromine, Cadmium, Chromium, Chlorine, Cobalt, Fluorine, Iodine,Manganese, Molybdenum Nickel, Phosphorus, Selenium, Silicon, Vanadium,Zinc, Amino Acids, Vitamin A, Vitamin D, Vitamin E, Vitamin K, VitaminC, Vitamin B complex, Thiamine (Vitamin 31), Riboflavin (Vitamin 132).Niacin (Vitamin B3), Pyridoxine (Vitamin B6), Biotin, Pantothenic Acidand Pantethine, Folic Acid, Vitamin B12, “Unofficial” B Vitaminsincluding Choline and Inositol, and Vitamin P (bioflavonoids).
 29. Thecomposition of claim 25 wherein the nutritional supplement comprises anelectrolyte.
 30. The composition of claim 25 wherein the nutritionalsupplement comprises a vitamin.
 31. The composition of claim 25 whereinthe film layer comprises one or more of pullulan, modified starch,pectin, carageenan, a maltrodextrin or alginate.
 32. The composition ofclaim 25 wherein the film layer comprises a natural or synthetic watersoluble polymer.
 33. A composition comprising: a film layer wherein thefilm layer rapidly dissolves in an oral cavity; and a coating comprisinga powder matrix; wherein the coating is applied to at least one side ofthe film layer and wherein the powder matrix comprises a nutritionalsupplement, an adhesive, a bulking agent, a flow agent, and a sweetener.34. The composition of claim 33 wherein the film layer dissolves withinthirty seconds of being placed in the oral cavity.
 35. The compositionof claim 33 wherein the film layer dissolves within fifteen seconds ofbeing placed in the oral cavity.
 36. The composition of claim 33 whereinthe nutritional supplement is selected from the group consisting ofIron, Sodium, Calcium, Magnesium, Carbohydrates, Proteins, Molybdenum,Copper, Potassium, Manganese, Chlorides, Bicarbonate and Carbonate,Aluminium, Arsenic, Bromine, Cadmium, Chromium, Chlorine, Cobalt,Fluorine, Iodine, Manganese, Molybdenum Nickel, Phosphorus, Selenium,Silicon, Vanadium, Zinc, Amino Acids, Vitamin A, Vitamin D, Vitamin E,Vitamin K, Vitamin C, Vitamin B complex, Thiamine (Vitamin 31),Riboflavin (Vitamin 132). Niacin (Vitamin B3), Pyridoxine (Vitamin B6),Biotin, Pantothenic Acid and Pantethine, Folic Acid, Vitamin B12,“Unofficial” B Vitamins including Choline and Inositol, Vitamin P(bioflavonoids).
 37. The composition of claim 33 wherein the nutritionalsupplement comprises an electrolyte.
 38. A method of manufacturing arapidly dissolving thin film comprising the steps of: providing a filmlayer; applying a coating to said film layer wherein the coatingcomprises a powder matrix and wherein the powder matrix comprises anutritional supplement, an adhesive, a bulking agent, a flow agent, anda sweetener.
 39. The method of claim 38 wherein the film layer dissolveswithin fifteen seconds of being placed in the oral cavity.
 40. Themethod of claim 38 further comprising the step of drying the film layerand powder matrix.
 41. The method of claim 40 wherein the step of dryingis at a temperature at about the softening point of the flow agent. 42.The method of claim 38 wherein the flow agent comprises a lipid, wax orpolyol.
 43. The method of claim 38 wherein the nutritional supplement isselected from the group consisting of Iron, Sodium, Calcium, Magnesium,Carbohydrates, Proteins, Molybdenum, Copper, Potassium, Manganese,Chlorides, Bicarbonate and Carbonate, Aluminium, Arsenic, Bromine,Cadmium, Chromium, Chlorine, Cobalt, Fluorine, Iodine, Manganese,Molybdenum Nickel, Phosphorus, Selenium, Silicon, Vanadium, Zinc, AminoAcids, Vitamin A, Vitamin D, Vitamin E, Vitamin K, Vitamin C, Vitamin Bcomplex, Thiamine (Vitamin 31), Riboflavin (Vitamin 132). Niacin(Vitamin B3), Pyridoxine (Vitamin B6), Biotin, Pantothenic Acid andPantethine, Folic Acid, Vitamin B12, “Unofficial” B Vitamins includingCholine and Inositol, and Vitamin P (bioflavonoids).
 44. The method ofclaim 38 wherein the nutritional supplement comprises an electrolyte.45. The method of claim 38 wherein the nutritional supplement comprisesa vitamin.
 46. The method of claim 38 further comprising the step ofpreparing the coating in a fluidized bed.
 47. The method of claim 38wherein the coating is applied by sifting, screening, atomization,static or mechanical agitation.
 48. The method of claim 38 wherein thepowder particles are charged.
 49. The method of claim 48 wherein thecoating is applied using a static spray gun.
 50. The method of claim 49wherein the static spray gun charges the powder particles such that thepowder particles adhere to the surface of the film layer.